Compounds having ortho-dimethyl heteroaromatic rings have been used in drug discover)/research, such as a drug for stroke, tetramethylpyrazine (Patent Literature 1) and a drug for ulcers, revaprazan (Patent Literatures 1 and 2).
However, two things are possibly concealed in use of those compounds having ortho-dimethyl heteroaromatic rings in research for development of new drugs. One of the conceals is a reduction in the water solubility of the compound as a result of introduction of a methyl group into two adjacent atoms foaling the ring (ortho-dimethyl group). It is usually known that the introduction of a methyl group into the compound increases the lipophilicity of the compound (Non Patent Literature 1). It is usually known that the water solubility of a compound is related with the absorption of orally administered drugs, and an increase in the lipophilicity of the compound or a reduction in the water solubility thereof may lower the absorption of drugs (Non Patent Literature 2). The other conceal is a reduction in metabolic stability. As shown in Non Patent Literatures 3 and 4, major metabolic reactions may occur in the moiety of the ortho-dimethyl group in the case of an aromatic or heteroaromatic ring substituted by an ortho-dimethyl group, and it is shown that the moiety of the ortho-dimethyl group is quickly metabolized and the half-life becomes short in humans in the case of the drug for stroke, tetramethylpyrazine (Non Patent Literature 5).
For this reason, novel bioisosteres of the heteroaromatic compounds having an ortho-dimethyl group, namely, compounds having the same pharmacological effects and having reduced concerns about the reduction in water solubility and the reduction in metabolic stability have been required, and furthermore, compounds used as synthetic intermediates for the novel bioisosteres have also been required.
Meanwhile, the compounds described in Patent Literatures 3 and 4 and Non Patent Literatures 6 to 9 are known as compounds similar to the compounds according to the invention of the present application; however, synthesizable heterocyclic rings and substituents thereof have been limited using multi-step synthetic procedures. As a result, there is a limit to synthesize heterocyclic rings having a wide variety of substituents.